Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 500,000 incident cancers worldwide. The treatment of HNSCC, combinations of surgery, radiation and chemotherapy, often result in significant morbidity and substantial healthcare costs. Elimination of the initial tumor offers the best chance of cure, yet we succeed only 50 percent of the time. Therapy fails most often due to recurrence at the primary site or in the neck, and less often from distant metastases. When initial or recurrent tumors are identified early, treatment outcome is better. Unfortunately the majority of HNSCC are identified in later stage. A marker for HNSCC that is able to detect new cancers and recurrences in early stages would be useful. CD44 may be a molecular marker of malignancy in other tissues and is detectable in body fluids in soluble form (solCD44). Our preliminary data suggest that solCD44 is increased in the saliva of HNSCC tumor patients compared to controls. In this study we will examine the expression of solCD44 in both newly diagnosed HNSCC patients and controls and in HNSCC patients with recurrence or second primaries. We will use a solCD44 ELISA test and a protein assay to evaluate the expression of solCD44 in HNSCC patient's saliva (aim 1). We will compare these to sol CD44 levels in controls that are matched for age, sex, race, socioeconomic status, tobacco and alcohol use. We will use the same assays to evaluate the expression of solCD44 in patients with recurrent or second primary HNSCC matching for previous treatment, original stage, tobacco and alcohol use (aim 2). The results of these studies will determine the validity of soICD44 ELISA test as a screening test for HNSCC.